Circular RNA FOXP1 relieves trophoblastic cell dysfunction in recurrent pregnancy loss via the miR-143-3p/S100A11 cascade

• Published in: Bioengineered Vol. 12; no. 1; pp. 9081 - 9093
• Main Authors: Gao, Yuan, Tang, Yukun, Sun, Qian, Guan, Guixue, Wu, Xiaoyan, Shi, Fan, Zhou, Zihao, Yang, Wen
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2021
• Subjects: Abortion, Habitual - genetics; Abortion, Habitual - metabolism; Abortion, Habitual - pathology; Case-Control Studies; Cell Movement; Cell Proliferation; Circfoxp1; Epithelial-Mesenchymal Transition; epithelial-to-mesenchymal transition; Female; Forkhead Transcription Factors - genetics; Gene Expression Regulation; Humans; MicroRNAs - genetics; miR-143-3p; Pregnancy; recurrent pregnancy loss; Repressor Proteins - genetics; Research Paper; RNA, Circular - genetics; S100 Proteins - genetics; S100 Proteins - metabolism; S100A11; Trophoblasts - metabolism; Trophoblasts - pathology; miR–143–3p; Circfoxp1; S100A11; recurrent pregnancy loss; epithelial-to-mesenchymal transition
• ISSN: 2165-5979; 2165-5987
• DOI: 10.1080/21655979.2021.1988374

Recurrent pregnancy loss (RPL) is closely associated with insufficient functions of trophoblastic cells. Circular RNA forkhead box P1 (circFOXP1) can regulate cell activities in different types of diseases. However, its effects on trophoblastic cells and its role in RPL development remain unknown. In this study, gene expressions were detected by RT-qPCR. Protein levels were detected by Western blotting. Trophoblastic cell viability, apoptosis, invasion, and migration were respectively analyzed via CCK-8, flow cytometry, wound healing, and transwell assays. The association between miR-143-3p and circFOXP1 or S100A11 (S100 calcium binding protein A11) was explored and confirmed by bioinformatics prediction and luciferase reporter assay. Herein, miR-143-3p was upregulated in RPL. Furthermore, miR-143-3p upregulation induced apoptosis and suppressed proliferation, epithelial-to-mesenchymal transition (EMT) process, and metastatic capabilities of trophoblastic cells; whereas, miR-143-3p inhibition exert opposite effects. MiR-143-3p targeted S100A11 and was adversely regulated by circFOXP1 expression. S100A11 inhibition partially offset the effect of miR-143-3p knockdown on trophoblastic cell viability, apoptosis, EMT, invasion, and migration. In addition, circFOXP1 competitively combined with miR-143-3p, thus regulating S100A11 expression. Moreover, circFOXP1 regulated trophoblastic cell functions through the miR-143-3p/S100A11 cascade. To sum up, our study, for the first time, demonstrated that circFOXP1 could improve dysfunction of trophoblastic cells through the miR-143-3p/S100A11 axis, providing novel biomarkers and diagnostic targets for RPL.